Functionally graded titanium implants: Characteristic enhancement induced by combined severe plastic deformation

Commercially pure titanium was processed by equal channel angular pressing (ECAP) and surface mechanical attrition treatment (SMAT) for the purpose of developing functionally graded titanium used for implants and a gradient structure including nanostructured, deformed and undeformed zones were produced on the samples. In particular, it was aimed to design the gradient-structure in the titanium with enhanced properties by applying 4 ECAP passes to form bulk structure of ultrafine-grains and subsequently subjecting SMAT to the surface of ECAPed samples to produce nanostructured surface region. Microstructural examination was made by electron back scatter diffraction (EBSD). Also, microhardness, nanoindentation, topography, roughness and wettability were evaluated. To examine the biological response, human osteosarcoma cells were cultured in contact with the samples in various time periods and morphology change, cell viability and alkaline phosphate activity were conducted also cell morphology was monitored. EBSD showed development of ultrafine-grained structure after 4 passes of ECAP with an average grain size of 500 nm. Applying SMAT resulted in additional refinement in the ECAP samples, particularly in the subsurface regions to a depth of 112 μm. Furthermore, the SMATed samples showed an enhancement in roughness, wettability and hardness magnitudes. Viability enhanced up to 7% in SMATed + ECAPed sample, although the acceptable cell adhesion, improved cell differentiation and mineralization were seen. The combined use of ECAP and SMAT has shown a good potential for optimizing the design of modern functionally graded medical devices and implants

Effect of Pioglitazone on Antioxidant Capacity and Oxidative Damage after Spinal Cord Injury in Rat

BACKGROUND AND OBJECTIVE: Reduction of the antioxidant capacity and oxidative damage has a crucial role in development of damage after spinal cord injury. Since pioglitazone (PPAR-gamma agonist) have a powerful antioxidant property, the present study aimed to evaluate the effect of pioglitazone on antioxidant capacity and oxidative damage in the injured areas of spinal cord in rat. METHODS: In the present experimental study eighteen male Wistar rats divided into three groups as follow (n=6); sham, control injured and pioglitazone-treated injured group. Spinal cord injury was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours until a week. At the end, malondialdehyde level, activity of catalase and superoxide dismutase (SOD) enzymes and also histopathological alterations of spinal cord were assessed. FINDINGS: Induction of spinal cord injury in control injured animals significantly increased the malondialdehyde levels (56%) and decreased the activity of catalase (48%) and SOD (65%) enzymes compared to sham group (p=0.004, p=0.001 and P=0.008, respectively). Pioglitazone in treated injured group significantly decreased the malondialdehyde levels (38%) and increased the activity of catalase (34%) enzyme compared to control injured group (p=0.038 and p=0.014, respectively). Also, pioglitazone prevented the histopathological changes of injured areas in spinal cord. CONCLUSION: The findings of present study indicate that treatment with pioglitazone through potentiation of the antioxidant defense capacity of injured spinal cord decreases oxidative damage and also histopathological changes of spinal cord

Increased male reproductive success in Ts65Dn “Down syndrome” mice

The Ts65Dn mouse is trisomic for orthologs of about half the genes on Hsa21. A number of phenotypes in these trisomic mice parallel those in humans with trisomy 21 (Down syndrome), including cognitive deficits due to hippocampal malfunction that are sufficiently similar to human that “therapies” developed in Ts65Dn mice are making their way to human clinical trials. However, the impact of the model is limited by availability. Ts65Dn cannot be completely inbred and males are generally considered to be sterile. Females have few, small litters and they exhibit poor care of offspring, frequently abandoning entire litters. Here we report identification and selective breeding of rare fertile males from two working colonies of Ts65Dn mice. Trisomic offspring can be propagated by natural matings or by in vitro fertilization (IVF) to produce large cohorts of closely related siblings. The use of a robust euploid strain as recipients of fertilized embryos in IVF or as the female in natural matings greatly improves husbandry. Extra zygotes cultured to the blastocyst stage were used to create trisomic and euploid embryonic stem (ES) cells from littermates. We developed parameters for cryopreserving sperm from Ts65Dn males and used it to produce trisomic offspring by IVF. Use of cryopreserved sperm provides additional flexibility in the choice of oocyte donors from different genetic backgrounds, facilitating rapid production of complex crosses. This approach greatly increases the power of this important trisomic model to interrogate modifying effects of trisomic or disomic genes that contribute to trisomic phenotypes

Lowering β-Amyloid Levels Rescues Learning and Memory in a Down Syndrome Mouse Model

β-amyloid levels are elevated in Down syndrome (DS) patients throughout life and are believed to cause Alzheimer's disease (AD) in adult members of this population. However, it is not known if β-amyloid contributes to intellectual disability in younger individuals. We used a γ-secretase inhibitor to lower β-amyloid levels in young mice that model DS. This treatment corrected learning deficits characteristic of these mice, suggesting that β-amyloid-lowering therapies might improve cognitive function in young DS patients

Chemical composition of nanoporous layer formed by electrochemical etching of p-type GaAs

Abstract : We have performed a detailed characterization study of electrochemically etched p-type GaAs in a hydrofluoric acid-based electrolyte. The samples were investigated and characterized through cathodoluminescence (CL), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). It was found that after electrochemical etching, the porous layer showed a major decrease in the CL intensity and a change in chemical composition and in the crystalline phase. Contrary to previous reports on p-GaAs porosification, which stated that the formed layer is composed of porous GaAs, we report evidence that the porous layer is in fact mainly constituted of porous As2O3. Finally, a qualitative model is proposed to explain the porous As2O3 layer formation on p-GaAs substrate

The power of comparative and developmental studies for mouse models of Down syndrome

Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

Alzheimer disease models and human neuropathology: similarities and differences

Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Aβ peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Aβ peptide, similar but not identical to the Aβ peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Aβ, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Aβ 42 levels, except for the Arctic mutation, which alters the Aβ sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Aβ deposition in most mouse lines. Doubly (APP × mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Aβ. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Aβ oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau −/− background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Aβ or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis